MOLECULAR GATEKEEPER MAY HELP BRAIN CREATE MEMORY

Johns Hopkins scientists have discovered that a common molecule in nerve
cells can shut important cell "gates," stemming a flow of calcium involved in
creating memory that also can contribute to stroke damage.

The discovery advances efforts to understand how the brain creates memories
by altering nerve cells, and may lead to new possibilities for treatment of
strokes and other disorders, according to Michael Ehlers, a Johns Hopkins
M.D./Ph.D. student. Ehlers won a Hopkins Young Investigators' Day Award for
his role in the new discovery.

Working in the labs of Richard Huganir, Ph.D., a Hopkins professor of
neuroscience, Ehlers learned that calmodulin, a molecule common to nerve cells,
can slam shut gates on the surface of nerve cells that allow chemicals to flow
into the cells.

When these gates, called NMDA glutamate receptors, open briefly, nerve cells
are stimulated, producing a chain reaction that results in the creation or
transmission of a message to another nerve cell.

If the nerves are rapidly stimulated in a short period of time, a magnesium
"bolt" can be knocked off the gate, allowing calcium ions to flow more freely
into the nerve. Depending on how many calcium ions flow in, the nerve cell may
become a quicker and stronger transmitter of messages or a slower and weaker
transmitter. Scientists call this synaptic plasticity, and believe it is an
important way the brain creates learning and memory.

"Now that we know that calmodulin can affect this process, this could
provide us with a possible mechanism for controlling whether nerves become
stronger or weaker transmitters of messages. This might one day help us
improve learning and memory," says Ehlers.

Researchers also think that NMDA receptors jam during a stroke in their full
open position, allowing the nerve cell to absorb a fatal dose of calcium.
Because calmodulin is found in most nerve cells, it may be a potent tool for
researchers trying to close NMDA receptors and
prevent nerve cell death.

Funding for Ehlers' work was provided by the National Institutes of Health
and the Howard Hughes Medical Institute.